基于TCGA数据库的胃腺癌铜死亡相关lncRNA预后模型构建

Establishment of cuproptosis-related lncRNA predicting model for prognosis of gastric adenocarcinoma based on TCGA database

目的基于癌症基因组图谱(TCGA)数据库建立胃腺癌的铜死亡相关长链非编码RNA(lncRNA)预后模型。方法从TCGA数据库中获取胃腺癌的转录组数据和临床数据,检索相关文献获取铜死亡相关基因,应用Pearson相关分析确定胃腺癌铜死亡相关lncRNA。对目标lncRNA进行单因素Cox和套索算法回归分析,筛选出预后相关lncRNA,然后对其进行多因素Cox回归分析,根据预后模型公式计算风险评分,将患者分成高、低风险组进行生存差异分析。通过Kaplan-Meier曲线、主成分分析、ROC曲线、列线图评价预后模型的预测效能。对高、低风险组进行肿瘤微环境(TME)、肿瘤突变负荷(TMB)、微卫星状态、免疫逃逸和药物敏感性分析。结果10个lncRNA被纳入构建预后模型,通过预后模型对样本进行生存分析发现,高风险组患者生存状况较差。主成分分析、ROC曲线证实该预后模型具有更高的灵敏度和准确度。单因素和多因素Cox回归分析显示年龄、临床分期和风险评分是预后的独立因子,以上述独立预后因子构建的列线图具有良好的区分度和一致性。进一步研究发现高风险组患者表现出更高的免疫浸润、低TMB、高度微卫星不稳定,并且高TMB和低风险的患者具有更好的预后。低风险组患者对更多的药物敏感,并且从免疫治疗中获益更多。结论铜死亡相关lncRNA构建的预后模型可预测胃腺癌患者的预后,同时可反映患者TME及免疫治疗获益情况,从而为胃腺癌患者的药物选择提供参考依据。

Objective To establish a cuproptosis-related long non-coding RNA(lncRNA)predicting model for prognosis of gastric adenocarcinoma based on The Cancer Genome Atlas(TCGA)database.Methods The transcriptome data and clinical data of gastric adenocarcinoma were obtained from TCGA database,and the relevant literature was searched to obtain cuproptosis-related genes.The lncRNAs associated with cuproptosis in gastric adenocarcinoma were screened by Pearson correlation,analyzed with univariate COX and LASSO regression analysis.Prognosis-related lncRNA were included into the multivariate COX proportional hazard model.The risk score was calculated,and the patients were divided into high and low risk groups for survival analysis.The predictive ability of the model was evaluated with Kaplan-Meier curve,principal component analysis(PCA),receiver operating characteristic(ROC)curve and nomogram.Tumor microenvironment(TME),tumor mutation burden(TMB),microsatellite status,immune escape and drug sensitivity analysis were performed in high and low risk groups.Results Ten lncRNAs were identified to construct prognosis model.Survival analysis showed that the patients in high risk group had poor survival status.PCA and ROC curve confirmed that the constructed prognostic model had higher sensitivity and accuracy.Univariate and multivariate COX regression analysis showed that age,clinical stage and risk score were independent prognostic factors.The nomogram was constructed with the above independent prognostic factors,and it had good discrimination and consistency.Further studies found that patients in the high risk group showed higher immune infiltration,low TMB,high microsatellite instability,and patients with high TMB and low risk had better prognosis.Patients in the low risk group were sensitive to more drugs and could benefit more from immunotherapy.Conclusion The prognostic model constructed by cuproptosis-related lncRNA can predict the prognosis of gastric adenocarcinoma patients,reflect the TME and the efficacy of immunotherapy in the patients,and provide a new reference for drug selection of gastric adenocarcinoma patients.